A diagnosis of gestational diabetes mellitus (GDM)has significant implications for the future health of the mother. GDM is often the culmination of years of unrecognized and unmodified diabetes risk factors that lead to overt and occult clinical manifestations during pregnancy. Systematic reviews of older studies conclude that 35-60% women with gestational diabetes will develop type 2 diabetes (DM2) at rates much greater than control groups who did not have glucose intolerance during pregnancy. Liraglutide may potentially delay disease progression in GDM considering the beta -(ß-)cell function improvement in DM2 and ß-cell mass shown to increase in animal models. This study will examine if the addition of liraglutide to metformin therapy is more effective than metformin alone in improving insulin sensitivity and normalizing insulin secretion in at-risk overweight/obese women with prior GDM.

An index of insulin secretion in relation to insulin resistance (IS-SI) will be calculated [ Time Frame: Change in index from baseline at 32-36 weeks,at 56 -60 weeks, and at study end (80-84 weeks) ] [ Designated as safety issue: No ]

Indexes of insulin sensitivity and secretion using the serum glucose and insulin concentrations obtained in the fasting state and during the 2hr OGTT with INS will be computed by several measures previously validated in women

Anthropometric measurements [ Time Frame: Change in measures of total and central adiposity from baseline at 32-36 weeks,at 56 -60 weeks, and at study end (80-84 weeks) ] [ Designated as safety issue: No ]

Development of dysglycemia [ Time Frame: Changes in glucose tolerance will be evaluated at baseline, at 32-36 weeks, at 56-60 weeks and at study end (80-84 weeks) ] [ Designated as safety issue: No ]

Change in glycemic status from baseline. at 32-36 weeks, 56-60 weeks and at study end(80-84 weeks). Dysglycemia will be defined as impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined IFG/IGT and diabetic according to the American Diabetes Association. Patients diagnosed with diabetes will be withdrawn and referred to a specialized physician.

Gestational diabetes is often the culmination of years of unrecognized and unmodified diabetes risk factors that lead to overt and occult clinical manifestations during pregnancy. . Despite the high and increasing rate of type 2 diabetes in Louisiana, the medical community does not have reliable estimates of the number of woman living in southern Louisiana who develop diabetes subsequent to GDM. Systematic reviews of older studies conclude that 35-60% women with gestational diabetes will develop type 2 diabetes at rates much greater than control groups who did not have glucose intolerance during pregnancy. The higher rates were in studies of particular ethnic groups in the U.S. Recently, follow-up programs elsewhere also have identified increasing rates of type 2 diabetes by 5-10 years after GDM: 9-43% type 2 diabetes in Europe and 11-21% in Asia. The frequency of type 2 diabetes is influenced by BMI, weight gain after pregnancy, family history of diabetes, fasting and postchallenge glucose levels during and after pregnancy, postpartum insulin resistance and inadequate β-cell secretion, and the need for pharmacological treatment during pregnancy. However, the risk factors are unable to predict all cases of subsequent type 2 diabetes: the biggest risk factor is a GDM pregnancy. Presently, in the literature, there are described new, more efficient methods of diabetes prevention in groups with a high risk of this disorder, which involve both, lifestyle modification and pharmacological therapies. Lifestyle intervention was found to reduce the incidence of type 2 diabetes by 58% and metformin by 31% as compared with placebo. The use of rosiglitazone in subjects with prediabetes resulted in a 60% reduction of the diabetes incidence rate. Studies are needed for optimal postpartum and long-term health of women who have had GDM. Considerable recent evidence suggests that incretin-based therapies may be useful for the treatment of DM2 because continuous administration of glucagon-like peptide 1 (GLP-1) produces substantial improvements in glucose control and ß-cell function in subjects with type 2 diabetes. Infusion of GLP-1 improves first and second-phase insulin secretion suggesting that early GLP-1 therapy may preserve ß-cell function in subjects with IGT or mild DM2. Whereas native GLP-1 has a very short half-life, the GLP-1 analogue liraglutide has a prolonged action (t1/2=13 h) suitable for once-daily injection. Liraglutide may potentially delay disease progression in GDM considering the ß-cell function improvement in DM2 and ß-cell mass shown to increase in animal models. This study will examine if the addition of liraglutide to metformin therapy is more effective than metformin alone in improving metabolic parameters in at-risk overweight/obese women with prior GDM

Eligibility

Ages Eligible for Study:

18 Years to 45 Years

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Adult female 18 years to 45 years of age who experienced GDM within 52 weeks of index pregnancy

Fasting serum triglycerides ≥800 mg/dl at screening. Lipid-lowering medications must have been maintained at the same dose for 3 months prior to enrollment

Hematological profiles considered to be clinically significant

Cholestasis during the past pregnancy

Presence of contradictions for GLP-1 receptor agonist or metformin administration such as allergy or hypersensitivity

Current use of metformin, thiazolidinediones, dipeptidyl peptidase-4 inhibitors or GLP-1 receptor agonist medications.

Use of drugs known to exacerbate glucose tolerance.

Use of prescription or over-the-counter weight-loss drugs

Diabetes postpartum or history of diabetes or prior use of medications to treat diabetes except gestational diabetes

Creatinine clearance less than 60 ml/min

History or currently undergoing chemotherapy or radiotherapy for cancer

Pregnancy planned during the coming two years

Currently breastfeeding

Exclusion criteria include any condition, which in the opinion of the investigator would place the subject at increased risk or otherwise make the subject unsuitable for participation in the study

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01234649